Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders appear to arise, in some cases, as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms onset or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The subgroup shares several common clinical characteristics in common, and also may share a common pathophysiology for their symptoms. Investigations of the nature and treatment of this novel subgroup are ongoing. In addition, studies of Sydenham's chorea (the neurological manifestation of rheumatic fever) are continuing to determine the nature of the post-streptococcal autoimmunity, as well as to identify more effective treatment strategies. During this reporting period, a paper was published in Lancet describing the efficacy of two immunomodulatory treatments - therapeutic plasma exchange and intravenous immunoglobulin (IVIG) for children with acute, severe OCD and tics. Both IVIG and plasma exchange were strikingly and significantly superior to placebo, with the average improvement exceeding 50% on some measures at one-month follow-up. Improvements were sustained at one year follow-up evaluations, as well. The mechanism of action of therapeutic plasma exchange is currently under investigation in the PANDAS cohort. We also published the results of an eight month long double-blind crossover trial of penicillin prophylaxis (vs. placebo) for prevention of symptom exacerbations in children with PANDAS. Fourteen children had GABHS infections during the penicillin phase, which contributed to a failure to demonstrate superiority of the active treatment. Not only did this confirm that neuropsychiatric symptom exacerbations can be triggered by GABHS infections, but it also raises the larger question of the utility of oral penicillin prophylaxis (for rheumatic fever.) A study is currently underway to determine whether a more effective oral agent might be successful in preventing post-streptococcal symptom exacerbations. Other investigations include a longitudinal, school-based assessment of tic and GABHS frequencies, and a placebo-controlled trial of amoxicillin therapy.